Is Cymbalta (duloxetine) safe during pregnancy?

From the Guidelines

Cymbalta (duloxetine) should be used during pregnancy only if the potential benefits outweigh the risks, and this decision should be made in consultation with a healthcare provider. The medication is classified as pregnancy category C, meaning that animal studies have shown adverse effects on the fetus, but there are no adequate well-controlled studies in humans. According to a recent study 1, the research to date should provide women considering antidepressant use during pregnancy reassurance because it suggests intrauterine antidepressant exposure does not substantially increase the risk for two concerning neurodevelopmental problems -- ASD and ADHD. However, some research suggests a small increased risk of postpartum hemorrhage and potential neonatal complications when Cymbalta is used late in pregnancy, including withdrawal symptoms, respiratory distress, and feeding difficulties in newborns 1.

If you're currently taking Cymbalta and discover you're pregnant, don't stop the medication abruptly as this can cause withdrawal symptoms; instead, speak with your doctor immediately about your options. For women with depression or anxiety during pregnancy, the risks of untreated mental health conditions must be weighed against potential medication risks. The American Psychiatric Association and the American College of Obstetricians and Gynecologists have published recommendations about decision-making regarding antidepressant treatment during pregnancy, suggesting that women with a history of severe suicide attempts or severe depression who have previously experienced symptom reduction with antidepressant treatment may respond to antidepressants better than psychotherapy 1.

Key considerations for the use of Cymbalta during pregnancy include:

• The severity of current symptoms
• Previous mental health history
• Patient treatment preferences
• The potential risks and benefits of treatment Regular monitoring throughout pregnancy is essential if you continue taking this medication. Your doctor might consider alternative treatments with better-established safety profiles during pregnancy, or may determine that continuing Cymbalta is appropriate based on your specific situation.

From the FDA Drug Label

In rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (MRHD) of 120 mg/day given to adolescents on a mg/m 2 basis When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m 2 basis The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U. S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data from a postmarketing retrospective cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% CI: 1.08 to 2. 18). Neonates exposed to duloxetine delayed-release capsules and other SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.

Cymbalta Safety in Pregnancy:

• The use of Cymbalta (duloxetine) during pregnancy may be associated with an increased risk of postpartum hemorrhage and neonatal complications.
• There is no clear evidence of a drug-associated risk of major birth defects or other adverse developmental outcomes.
• However, fetal weights were decreased in animal studies at doses up to 3 and 6 times the maximum recommended human dose.
• Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes.
• The estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively 2.
• Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants 2.
• Neonates exposed to duloxetine delayed-release capsules and other SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding 2.

From the Research

Cymbalta Safety in Pregnancy

• The safety of Cymbalta (duloxetine) during pregnancy is a concern due to the potential risks to the mother and the fetus 3, 4.
• Studies have shown that the use of duloxetine during pregnancy may be associated with an increased risk of spontaneous abortion, but no increase in other adverse outcomes such as major fetal malformations 4.
• Late-pregnancy exposure to duloxetine may be associated with poor neonatal adaptation syndrome, but the magnitude of this risk is not known 4.
• A study analyzing pregnancy outcome data from the Lilly Safety System and the FDA Adverse Events Reporting System found that the frequency of abnormal outcomes reported in duloxetine pregnancy cases is generally consistent with the historic control rates in the general population 3.

Comparison with Other Antidepressants

• A systematic review of meta-analyses found that antidepressant drugs, including duloxetine, may be associated with an increased risk of major congenital malformations, congenital heart defects, preterm birth, and neonatal adaptation symptoms 5.
• However, the review also found that the evidence for these associations is limited and that the risk of adverse outcomes may be influenced by factors such as maternal psychiatric disorders and antidepressant drug dosage 5.
• Another study found that SSRIs, a class of antidepressants that includes duloxetine, can still be considered as appropriate for use in pregnant or lactating women who require pharmacological treatment, as the abundant data support their relative safety 6.

Breastfeeding Considerations

• Duloxetine is excreted into breast milk, but the infant exposure is less than 1% of the maternal weight-adjusted dose, suggesting that duloxetine can be safely administered to a woman who is breastfeeding her infant 4, 7.
• A case study found no evidence of developmental or other type of toxicity in an infant exposed to duloxetine during the second half of gestation and during breast-feeding in the first 32 days after birth 7.